Utility of p16INK4a expression for the interpretation of uterine cervical biopsies in Kenya

Introduction: histologic interpretation of hematoxylin and eosin-stained cervical biopsies is subject to substantial discordance among pathologists. Immunohistochemical staining for p16INK4a can reduce inter-observer disagreement. We did a cross-sectional study to evaluate the utility of p16INK4a staining in the assessment of cervical biopsies in Nairobi, Kenya. Methods: hematoxylin and eosin-stained sections from 91 colposcopic biopsies diagnosed as negative for dysplasia or as cervical intraepithelial neoplasia (CIN) grade 1-3 from 2011-2013 in Nairobi, Kenya, were reviewed and immunostained for p16INK4a. Agreement in interpretation of cervical biopsies was compared between primary and consensus review results. Results: on primary evaluation, 16 cases were negative for squamous dysplasia; 23 were CIN 1; 37 CIN 2; and 15 CIN 3. On consensus review, 32 cases were negative for dysplasia; 19 were CIN 1; 16 CIN 2 and 24 CIN 3. Agreement was moderate between primary and consensus histology review results for the diagnosis of low-grade versus high-grade squamous intraepithelial lesions (Kappa = 0.568). None of the cases negative for dysplasia were positive for p16INK4a expression, but in primary and consensus review results, 17% and 5% cases of CIN 1; 49% and 69% of CIN 2, and 80% and 96% of CIN 3 were p16INK4a positive, respectively. Conclusion: there was significant variability in the interpretation of cervical biopsies on hematoxylin and eosin between primary and consensus review assessments. 75% of CIN 1 cases that were upgraded to CIN 2 during consensus review expressed p16INK4a. These findings demonstrate the role of p16INK4a in increasing diagnostic accuracy and as a marker of high-grade CIN 2/3

The potential of RNA as a target for national screening of pre-cancer

Whole national screening of pre-cancer is done only in some few countries, dominated by The Netherlands, Denmark, UK, Norway and Finland. This national screening are done combining national cancer registry, national public health and national medical bodies or hospitals. Until some few years ago national screening was only done using morphological or visual methods or technology. Today a number of molecular methods have been implemented to serve these national screening programs. Based on all the discussions within this review, it is clear that the main driving engine and the cause of cervical pre-cancer and the main cause of invasive cervical cancer is the expression of E6 and E7 oncoproteins from HPV 16, 18, 31, 33 and 45. However, the main challenge is the role of morphology or imaging based diagnosis in the original definition of pre-cancer disease. This definition is not based on the cause of cervical pre-cancer but based on a complex morphological observation heavily based on subjective matters. The challenge between these two definitions are discussed in this review. The unique discovery done while validating the first standardized detection technology used against mRNA, confirmed that the presence of both abnormal E6 and/or E7 mRNA and protein is the cause of cervical pre-cancer or severe neoplasia and the main cause of invasive cervical cancer. This confirmation was evident even though all these studies were disturbed by the above biases from morphology or imaging based  diagnosis. The presence of the template for high production of the most carcinogenic compounds ever discovered, must cause a more accurate screening program. A number of studies have proved that the detection of E6/E7 mRNA followed-up by indirect or direct treatment in a well-organized national screening program would reduce the incidence of cervical cancer. This review discuss the main studies involved in the scientific, clinical evaluation and how this unique technology could be used as a new medical gold standard for national screening of cervical pre-cancer

The Impact of Human Immunodeficiency Virus and Human Papillomavirus Co-Infection on HPV Genotype Distribution and Cervical Lesion Grade in a Semi-Urban Population in Tigoni, Kenya

1. IntroductionCervical cancer is an important global public healthproblem and a common cause of death among women,and it is attributable to human papillomavirus (HPV)(Walboomers et al, 1999; Parkin et al, 2008). In a largeseries of invasive cervical cancer from around theworld, HPV-DNA was detected in 99.7% of the tumors,leading to the conclusion that HPV was a necessarycause of cervical cancer (Bosch et al, 1995; Walboomerset al, 1999; Bosch et al, 2007). The identification ofHPV’s role in cervical cancer has led to importantadvances in primary prevention through vaccinationand diagnosis through HPV detection (Stanley et al,2008; Bosch et al, 2008). However, tangible reductionin the incidence of cervical cancer and the impact onglobal public health will probably take decades. As HPVtypes are divergent, efficacy of current vaccines is typerestricted,and therefore development of the nextgeneration of HPV vaccines will require inclusion ofrelevant antigens from several HPV types (Lowy, 2008).Geographical profiling of HPV type distribution will beimportant in making vaccines more relevant for targetpopulations.Most women will be infected with HPV sometime intheir lifetime. Results from large meta-analyses studiesindicate that at any given point in time, 10.4% (95%confidence interval (CI) 10.2-10.7) of womenworldwide are positive for cervical HPV DNA (Bosch etal, 2008). The prevalence of HPV is higher in lessdeveloped regions (13.4%; 95% CI: 13.1-13.7) than inthe more developed regions (8.4%; 95% CI: 8.3-8.6)(Bosch et al, 2008). The same studies indicate thatAfrican women at 22.1% (95% CI: 20.9-23.4) and EastAfrican women in particular, have the highest HPVprevalence rates (31.6%; 95% CI: 29.5-33.8) (Bosch etal, 2008). HPV type 16 is the most common in allcontinents, with an estimated point prevalence of 2.6%(95% CI: 2.5-2.8) worldwide, and HPV type 18 thesecond most frequently detected type (Clifford et al,2005). Regional differences are thought to be related togeographical and immunogenetic factors, such asdefects in cellular immunity through chronic cervicalinflammation, malnutrition and more recently, HIVinfection; Type 16 though appears to be less influencedby immune impairment than other types (Clifford et al,2005).Although many women get infected with HPV, most donot develop cervical cancer. Several co-factors arepostulated to influence the disease process. Thepotential co-factors include exogenous factors such astobacco smoking, hormonal contraceptives, and coinfectionswith other sexually transmitted infections(Munoz et al, 2006). In addition, viral co-factors, suchspecific HPV types, viral load, and viral integration, aswell as host co-factors such as endogenous hormones,genetic factors, and factors related to the immuneresponse may variably influence the course of HPVinfection (Munoz et al, 2006).Women with HIV infection have been shown to be morelikely not only to have a concurrent HPV infection butalso to have an increased risk for a high grade cervicalsquamous intraepithelial lesion (La Ruche et al, 1998;Temmerman et al, 1999; Womack et al, 2000; Baay et al,2004; Hawes et al, 2006; Didelot-Rousseau et al, 2006;Ngándwe et al, 2007). HPV is the commonest sexuallytransmitted infection, with more than 75% of sexuallyactive adults acquiring one or more genotypes in theirlifetime (Bosch et al, 2008). However, by age 30 years,most women clear the infection due to an effective cellmediatedimmune response, and only a small numberthereafter are diagnosed with a HPV-associated lesion(Schiffman, 1992). It is thought that it is through itseffect on CD4+ cells and regulation of immuneresponses to a variety of antigens that HIV attenuatesthe systemic response to HPV (Palefsky, 2006).The prevalence of HIV among adult Kenyan women was13% in 2003 with trends reported to have decreased to5.1% by 2006 (KDHS, 2003). The high prevalence ofHIV may increase the incidence of cervical pre-cancerand potentially, of cervical cancer. Gichangi et al (2002),however, demonstrated that a two to three-foldincrease in HIV prevalence did not translate to aproportionate increment in incidence of cervical cancer.They hypothesized that HIV-infected women die fromHIV-related opportunistic infections before theydevelop invasive cervical cancer. The mean survivaltime for women with HIV in 2008 was reported to be 5years (Yamada et al, 2008) while typically more than 10years elapse before the development of cervical cancerafter HPV infection. Yamada et al (2008) also advancedthe possibility that sub-clinical cervical cancer may bemissed in many women dying prematurely from AIDSrelatedopportunistic infections.This study was carried out to establish whether the coinfectionof HIV and HPV has an influence on HPVgenotype distribution and on the prevalence and gradeof cervical neoplasia

The Impact of Human Immunodeficiency Virus and Human Papillomavirus Co-Infection on HPV Genotype Distribution and Cervical Lesion Grade in a Semi-Urban Population in Tigoni, Kenya

1. IntroductionCervical cancer is an important global public healthproblem and a common cause of death among women,and it is attributable to human papillomavirus (HPV)(Walboomers et al, 1999; Parkin et al, 2008). In a largeseries of invasive cervical cancer from around theworld, HPV-DNA was detected in 99.7% of the tumors,leading to the conclusion that HPV was a necessarycause of cervical cancer (Bosch et al, 1995; Walboomerset al, 1999; Bosch et al, 2007). The identification ofHPV’s role in cervical cancer has led to importantadvances in primary prevention through vaccinationand diagnosis through HPV detection (Stanley et al,2008; Bosch et al, 2008). However, tangible reductionin the incidence of cervical cancer and the impact onglobal public health will probably take decades. As HPVtypes are divergent, efficacy of current vaccines is typerestricted,and therefore development of the nextgeneration of HPV vaccines will require inclusion ofrelevant antigens from several HPV types (Lowy, 2008).Geographical profiling of HPV type distribution will beimportant in making vaccines more relevant for targetpopulations.Most women will be infected with HPV sometime intheir lifetime. Results from large meta-analyses studiesindicate that at any given point in time, 10.4% (95%confidence interval (CI) 10.2-10.7) of womenworldwide are positive for cervical HPV DNA (Bosch etal, 2008). The prevalence of HPV is higher in lessdeveloped regions (13.4%; 95% CI: 13.1-13.7) than inthe more developed regions (8.4%; 95% CI: 8.3-8.6)(Bosch et al, 2008). The same studies indicate thatAfrican women at 22.1% (95% CI: 20.9-23.4) and EastAfrican women in particular, have the highest HPVprevalence rates (31.6%; 95% CI: 29.5-33.8) (Bosch etal, 2008). HPV type 16 is the most common in allcontinents, with an estimated point prevalence of 2.6%(95% CI: 2.5-2.8) worldwide, and HPV type 18 thesecond most frequently detected type (Clifford et al,2005). Regional differences are thought to be related togeographical and immunogenetic factors, such asdefects in cellular immunity through chronic cervicalinflammation, malnutrition and more recently, HIVinfection; Type 16 though appears to be less influencedby immune impairment than other types (Clifford et al,2005).Although many women get infected with HPV, most donot develop cervical cancer. Several co-factors arepostulated to influence the disease process. Thepotential co-factors include exogenous factors such astobacco smoking, hormonal contraceptives, and coinfectionswith other sexually transmitted infections(Munoz et al, 2006). In addition, viral co-factors, suchspecific HPV types, viral load, and viral integration, aswell as host co-factors such as endogenous hormones,genetic factors, and factors related to the immuneresponse may variably influence the course of HPVinfection (Munoz et al, 2006).Women with HIV infection have been shown to be morelikely not only to have a concurrent HPV infection butalso to have an increased risk for a high grade cervicalsquamous intraepithelial lesion (La Ruche et al, 1998;Temmerman et al, 1999; Womack et al, 2000; Baay et al,2004; Hawes et al, 2006; Didelot-Rousseau et al, 2006;Ngándwe et al, 2007). HPV is the commonest sexuallytransmitted infection, with more than 75% of sexuallyactive adults acquiring one or more genotypes in theirlifetime (Bosch et al, 2008). However, by age 30 years,most women clear the infection due to an effective cellmediatedimmune response, and only a small numberthereafter are diagnosed with a HPV-associated lesion(Schiffman, 1992). It is thought that it is through itseffect on CD4+ cells and regulation of immuneresponses to a variety of antigens that HIV attenuatesthe systemic response to HPV (Palefsky, 2006).The prevalence of HIV among adult Kenyan women was13% in 2003 with trends reported to have decreased to5.1% by 2006 (KDHS, 2003). The high prevalence ofHIV may increase the incidence of cervical pre-cancerand potentially, of cervical cancer. Gichangi et al (2002),however, demonstrated that a two to three-foldincrease in HIV prevalence did not translate to aproportionate increment in incidence of cervical cancer.They hypothesized that HIV-infected women die fromHIV-related opportunistic infections before theydevelop invasive cervical cancer. The mean survivaltime for women with HIV in 2008 was reported to be 5years (Yamada et al, 2008) while typically more than 10years elapse before the development of cervical cancerafter HPV infection. Yamada et al (2008) also advancedthe possibility that sub-clinical cervical cancer may bemissed in many women dying prematurely from AIDSrelatedopportunistic infections.This study was carried out to establish whether the coinfectionof HIV and HPV has an influence on HPVgenotype distribution and on the prevalence and gradeof cervical neoplasia

Curriculum and training needs of mid-level health workers in Africa: a situational review from Kenya, Nigeria, South Africa and Uganda.

BACKGROUND: Africa's health systems rely on services provided by mid-level health workers (MLWs). Investment in their training is worthwhile since they are more likely to be retained in underserved areas, require shorter training courses and are less dependent on technology and investigations in their clinical practice than physicians. Their training programs and curricula need up-dating to be relevant to their practice and to reflect advances in health professional education. This study was conducted to review the training and curricula of MLWs in Kenya, Nigeria, South Africa and Uganda, to ascertain areas for improvement. METHODS: Key informants from professional associations, regulatory bodies, training institutions, labour organisations and government ministries were interviewed in each country. Policy documents and training curricula were reviewed for relevant content. Feedback was provided through stakeholder and participant meetings and comments recorded. 421 District managers and 975 MLWs from urban and rural government district health facilities completed self-administered questionnaires regarding MLW training and performance. RESULTS: Qualitative data indicated commonalities in scope of practice and in training programs across the four countries, with a focus on basic diagnosis and medical treatment. Older programs tended to be more didactic in their training approach and were often lacking in resources. Significant concerns regarding skills gaps and quality of training were raised. Nevertheless, quantitative data showed that most MLWs felt their basic training was adequate for the work they do. MLWs and district managers indicated that training methods needed updating with additional skills offered. MLWs wanted their training to include more problem-solving approaches and practical procedures that could be life-saving. CONCLUSIONS: MLWs are essential frontline workers in health services, not just a stop-gap. In Kenya, Nigeria and Uganda, their important role is appreciated by health service managers. At the same time, significant deficiencies in training program content and educational methodologies exist in these countries, whereas programs in South Africa appear to have benefited from their more recent origin. Improvements to training and curricula, based on international educational developments as well as the local burden of disease, will enable them to function with greater effectiveness and contribute to better quality care and outcomes

Task Sharing and Shifting to Provide Pathology Diagnostic Services: The Kenya Fine-Needle Aspiration Biopsy Cytology and Bone Marrow Aspiration and Trephine Biopsy Training Program

Purpose: Fine-needle aspiration biopsy (FNAB) cytology is a simple, inexpensive, and accurate diagnostic test for benign, infectious, and malignant lesions of the breast, thyroid, lymph nodes, and other organs. Similarly, bone marrow aspiration and trephine (BMAT) biopsy procedures are relatively simple and inexpensive techniques that are important for diagnosing and monitoring many hematologic diseases including leukemias and lymphomas. However, the scarcity of pathologists in Kenya limits patient access to these simple diagnostic tests. We describe a task sharing and shifting program that sought to improve the provision of FNABs and BMAT biopsies in tertiary public hospitals in Kenya. Methods: Between January 2016 and February 2017, we trained pathologists, pathology residents, and technologists from the University of Nairobi and Aga Khan University Hospital, Nairobi, in FNAB and BMAT biopsies, who in turn trained pathologists, medical officers (MO), clinical officers (CO), and technologists at five tertiary public hospitals. The program involved curriculum development, training workshops, the establishment of new and strengthening existing FNAB and BMAT biopsy clinics, interim site visits, audits, and stakeholder workshops. Results: Fifty-one medical personnel at the tertiary hospitals were trained. The FNAB numbers increased by 41% to 1,681, with 139 malignant diagnoses (7.1%). BMAT biopsy numbers increased by 268% to 140, with 34 malignant cases. Between 60% and 100% of the FNAB and BMAT biopsy procedures were performed by MO and CO over the project period. One new FNAB and two new BMAT biopsy clinics were established. Conclusion: This project demonstrates a successful model of task sharing and shifting from specialist pathologists to MO and CO that improved access to important FNAB and BMAT biopsy services in a low-resource setting

Institutional Factors Influencing Effective Teaching of Agriculture Subject in Public Secondary Schools in Tharaka Nithi County, Kenya

Abstract Effective teachers use a range of assessment data to differentiate the curriculum as needed and engage learners in purposeful learnin

Progesterone, Estradiol and their receptors in leiomyomata and the adjacent normal myometria of black Kenyan women

No abstract available [Afr. J. Health Sci. 2002; 9: 123-128

The prevalence of human papillomavirus infection in Mombasa, Kenya

Objectives A human papillomavirus (HPV) prevalence survey was done in Mombasa, Kenya, to improve the knowledge of HPV prevalence and genotype distribution in sub-Saharan African countries overall, and in women of different ages. Methods HPV prevalence was assessed using PCR in women older than 15 years attending family planning and mother-child care services. Results Among 496 women, HPV prevalence was high (42.3%; 95% CI: 37.9-46.8; world age-standardized). Moreover, 46% of HPV-positive women harbored multiple-type infections. The most common types were HPV58 (10.5% of women), HPV16 (7.7%), HPV53 (6.7%), HPV18 (4.6%), and HPV6 (4.4%), and the prevalence of any high-risk HPV type was 28.8%. HPV prevalence was elevated among all age-groups (range 36.4-45.7%). Independent associations with HPV positivity were found for being in a polygamous marriage (OR = 1.7) and lifetime number of sexual partners (OR for >= 3 vs. 1 = 1.5), although they were of only borderline statistical significance. Conclusions These findings differ from other world regions, showing a high HPV burden in all age-groups with a high proportion of multiple-type infections. Our data strengthen the urgency of HPV vaccination in Kenya but also highlight the elevated number of women who would have positive results in an HPV-based screening program in the country